PGS: a tool for association study of high-dimensional microRNA expression data with repeated measures.

MOTIVATION: MicroRNAs (miRNAs) are short single-stranded non-coding molecules that usually function as negative regulators to silence or suppress gene expression. Owning to the dynamic nature of miRNA and reduced microarray and sequencing costs, a growing number of researchers are now measuring high-dimensional miRNA expression data using repeated or multiple measures in which each individual has more than one sample collected and measured over time. However, the commonly used univariate association testing or the site-by-site (SBS) testing may underutilize the longitudinal feature of the data, leading to underpowered results and less biologically meaningful results. RESULTS: We propose a penalized regression model incorporating grid search method (PGS), for analyzing associations of high-dimensional miRNA expression data with repeated measures. The development of this analytical framework was motivated by a real-world miRNA dataset. Comparisons between PGS and the SBS testing revealed that PGS provided smaller phenotype prediction errors and higher enrichment of phenotype-related biological pathways than the SBS testing. Our extensive simulations showed that PGS provided more accurate estimates and higher sensitivity than the SBS testing with comparable specificities. AVAILABILITY AND IMPLEMENTATION: R source code for PGS algorithm, implementation example and simulation study are available for download at https://github.com/feizhe/PGS.

Design patterns for the development of electronic health record-driven phenotype extraction algorithms.

BACKGROUND: Design patterns, in the context of software development and ontologies, provide generalized approaches and guidance to solving commonly occurring problems, or addressing common situations typically informed by intuition, heuristics and experience. While the biomedical literature contains broad coverage of specific phenotype algorithm implementations, no work to date has attempted to generalize common approaches into design patterns, which may then be distributed to the informatics community to efficiently develop more accurate phenotype algorithms. METHODS: Using phenotyping algorithms stored in the Phenotype KnowledgeBase (PheKB), we conducted an independent iterative review to identify recurrent elements within the algorithm definitions. We extracted and generalized recurrent elements in these algorithms into candidate patterns. The authors then assessed the candidate patterns for validity by group consensus, and annotated them with attributes. RESULTS: A total of 24 electronic Medical Records and Genomics (eMERGE) phenotypes available in PheKB as of 1/25/2013 were downloaded and reviewed. From these, a total of 21 phenotyping patterns were identified, which are available as an online data supplement. CONCLUSIONS: Repeatable patterns within phenotyping algorithms exist, and when codified and cataloged may help to educate both experienced and novice algorithm developers. The dissemination and application of these patterns has the potential to decrease the time to develop algorithms, while improving portability and accuracy.

Characterizing variability of electronic health record-driven phenotype definitions.

OBJECTIVE: The aim of this study was to analyze a publicly available sample of rule-based phenotype definitions to characterize and evaluate the variability of logical constructs used. MATERIALS AND METHODS: A sample of 33 preexisting phenotype definitions used in research that are represented using Fast Healthcare Interoperability Resources and Clinical Quality Language (CQL) was analyzed using automated analysis of the computable representation of the CQL libraries. RESULTS: Most of the phenotype definitions include narrative descriptions and flowcharts, while few provide pseudocode or executable artifacts. Most use 4 or fewer medical terminologies. The number of codes used ranges from 5 to 6865, and value sets from 1 to 19. We found that the most common expressions used were literal, data, and logical expressions. Aggregate and arithmetic expressions are the least common. Expression depth ranges from 4 to 27. DISCUSSION: Despite the range of conditions, we found that all of the phenotype definitions consisted of logical criteria, representing both clinical and operational logic, and tabular data, consisting of codes from standard terminologies and keywords for natural language processing. The total number and variety of expressions are low, which may be to simplify implementation, or authors may limit complexity due to data availability constraints. CONCLUSIONS: The phenotype definitions analyzed show significant variation in specific logical, arithmetic, and other operators but are all composed of the same high-level components, namely tabular data and logical expressions. A standard representation for phenotype definitions should support these formats and be modular to support localization and shared logic.

Accelerating Food Allergy Research: Need for a Data Commons.

Food allergy is a significant health problem affecting approximately 8% of children and 11% of adults in the United States. It exhibits all the characteristics of a "complex" genetic trait; therefore, it is necessary to look at very large numbers of patients, far more than exist at any single organization, to eliminate gaps in the current understanding of this complex chronic disorder. Advances may be achieved by bringing together food allergy data from large numbers of patients into a Data Commons, a secure and efficient platform for researchers, comprising standardized data, available in a common interface for download and/or analysis, in accordance with the FAIR (Findable, Accessible, Interoperable, and Reusable) principles. Prior data commons initiatives indicate that research community consensus and support, formal food allergy ontology, data standards, an accepted platform and data management tools, an agreed upon infrastructure, and trusted governance are the foundation of any successful data commons. In this article, we will present the justification for the creation of a food allergy data commons and describe the core principles that can make it successful and sustainable.

Development of Food Allergy Data Dictionary: Toward a Food Allergy Data Commons.

BACKGROUND: Food allergy (FA) data lacks a common base of terminology and hinders data exchange among institutions. OBJECTIVE: To examine the current FA concept coverage by clinical terminologies and to develop and evaluate a Food Allergy Data Dictionary (FADD). METHODS: Allergy/immunology templates and patient intake forms from 4 academic medical centers with expertise in FA were systematically reviewed, and in-depth discussions with a panel of FA experts were conducted to identify important FA clinical concepts and data elements. The candidate ontology was iteratively refined through a series of virtual meetings. The concepts were mapped to existing clinical terminologies manually with the ATHENA vocabulary browser. Finally, the revised dictionary document was vetted with experts across 22 academic FA centers and 3 industry partners. RESULTS: A consensus version 1.0 FADD was finalized in November 2020. The FADD v1.0 contained 936 discrete FA concepts that were grouped into 14 categories. The categories included both FA-specific concepts, such as foods triggering reactions, and general health care categories, such as medications. Although many FA concepts are included in existing clinical terminologies, some critical concepts are missing. CONCLUSIONS: The FADD provides a pragmatic tool that can enable improved structured coding of FA data for both research and clinical uses, as well as lay the foundation for the development of standardized FA structured data entry forms.

Implementation of workflow engine technology to deliver basic clinical decision support functionality.

BACKGROUND: Workflow engine technology represents a new class of software with the ability to graphically model step-based knowledge. We present application of this novel technology to the domain of clinical decision support. Successful implementation of decision support within an electronic health record (EHR) remains an unsolved research challenge. Previous research efforts were mostly based on healthcare-specific representation standards and execution engines and did not reach wide adoption. We focus on two challenges in decision support systems: the ability to test decision logic on retrospective data prior prospective deployment and the challenge of user-friendly representation of clinical logic. RESULTS: We present our implementation of a workflow engine technology that addresses the two above-described challenges in delivering clinical decision support. Our system is based on a cross-industry standard of XML (extensible markup language) process definition language (XPDL). The core components of the system are a workflow editor for modeling clinical scenarios and a workflow engine for execution of those scenarios. We demonstrate, with an open-source and publicly available workflow suite, that clinical decision support logic can be executed on retrospective data. The same flowchart-based representation can also function in a prospective mode where the system can be integrated with an EHR system and respond to real-time clinical events. We limit the scope of our implementation to decision support content generation (which can be EHR system vendor independent). We do not focus on supporting complex decision support content delivery mechanisms due to lack of standardization of EHR systems in this area. We present results of our evaluation of the flowchart-based graphical notation as well as architectural evaluation of our implementation using an established evaluation framework for clinical decision support architecture. CONCLUSIONS: We describe an implementation of a free workflow technology software suite (available at http://code.google.com/p/healthflow) and its application in the domain of clinical decision support. Our implementation seamlessly supports clinical logic testing on retrospective data and offers a user-friendly knowledge representation paradigm. With the presented software implementation, we demonstrate that workflow engine technology can provide a decision support platform which evaluates well against an established clinical decision support architecture evaluation framework. Due to cross-industry usage of workflow engine technology, we can expect significant future functionality enhancements that will further improve the technology's capacity to serve as a clinical decision support platform.

Medical providers' dental information needs: a baseline survey.

Articulation of medical and dental practices has been strongly called for based on the many oral-systemic connections. With the rapid development and adoption of electronic health records, the feasibility of integrating medical and dental patient data should be strongly considered. The objective of this study was to develop an initial understanding of the medical providers' core dental information needs and opinion of integrated medical-dental electronic health record (iEHR) environment in their workflow. This was achieved by administering a 13 question survey to a group of 1,197 medical care providers employed by Marshfield Clinic in Wisconsin, United States. The survey received a response rate of 35%. The responses were analyzed based on provider 'Role' and 'Specialty'. The majority of the respondents felt the need for patient's dental information to coordinate or provide effective medical care. An integrated electronic health record environment could facilitate this holistic patient care approach.

A retrospective look at the predictions and recommendations from the 2009 AMIA policy meeting: did we see EHR-related clinician burnout coming?

Clinicians often attribute much of their burnout experience to use of the electronic health record, the adoption of which was greatly accelerated by the Health Information Technology for Economic and Clinical Health Act of 2009. That same year, AMIA's Policy Meeting focused on possible unintended consequences associated with rapid implementation of electronic health records, generating 17 potential consequences and 15 recommendations to address them. At the 2020 annual meeting of the American College of Medical Informatics (ACMI), ACMI fellows participated in a modified Delphi process to assess the accuracy of the 2009 predictions and the response to the recommendations. Among the findings, the fellows concluded that the degree of clinician burnout and its contributing factors, such as increased documentation requirements, were significantly underestimated. Conversely, problems related to identify theft and fraud were overestimated. Only 3 of the 15 recommendations were adjudged more than half-addressed.

Infobuttons for Genomic Medicine: Requirements and Barriers.

OBJECTIVES: The study aimed to understand potential barriers to the adoption of health information technology projects that are released as free and open source software (FOSS). METHODS: We conducted a survey of research consortia participants engaged in genomic medicine implementation to assess perceived institutional barriers to the adoption of three systems: ClinGen electronic health record (EHR) Toolkit, DocUBuild, and MyResults.org. The survey included eight barriers from the Consolidated Framework for Implementation Research (CFIR), with additional barriers identified from a qualitative analysis of open-ended responses. RESULTS: We analyzed responses from 24 research consortia participants from 18 institutions. In total, 14 categories of perceived barriers were evaluated, which were consistent with other observed barriers to FOSS adoption. The most frequent perceived barriers included lack of adaptability of the system, lack of institutional priority to implement, lack of trialability, lack of advantage of alternative systems, and complexity. CONCLUSION: In addition to understanding potential barriers, we recommend some strategies to address them (where possible), including considerations for genomic medicine. Overall, FOSS developers need to ensure systems are easy to trial and implement and need to clearly articulate benefits of their systems, especially when alternatives exist. Institutional champions will remain a critical component to prioritizing genomic medicine projects.

Planning for patient-reported outcome implementation: Development of decision tools and practical experience across four clinics.

INTRODUCTION: Many institutions are attempting to implement patient-reported outcome (PRO) measures. Because PROs often change clinical workflows significantly for patients and providers, implementation choices can have major impact. While various implementation guides exist, a stepwise list of decision points covering the full implementation process and drawing explicitly on a sociotechnical conceptual framework does not exist. METHODS: To facilitate real-world implementation of PROs in electronic health records (EHRs) for use in clinical practice, members of the EHR Access to Seamless Integration of Patient-Reported Outcomes Measurement Information System (PROMIS) Consortium developed structured PRO implementation planning tools. Each institution pilot tested the tools. Joint meetings led to the identification of critical sociotechnical success factors. RESULTS: Three tools were developed and tested: (1) a PRO Planning Guide summarizes the empirical knowledge and guidance about PRO implementation in routine clinical care; (2) a Decision Log allows decision tracking; and (3) an Implementation Plan Template simplifies creation of a sharable implementation plan. Seven lessons learned during implementation underscore the iterative nature of planning and the importance of the clinician champion, as well as the need to understand aims, manage implementation barriers, minimize disruption, provide ample discussion time, and continuously engage key stakeholders. CONCLUSIONS: Highly structured planning tools, informed by a sociotechnical perspective, enabled the construction of clear, clinic-specific plans. By developing and testing three reusable tools (freely available for immediate use), our project addressed the need for consolidated guidance and created new materials for PRO implementation planning. We identified seven important lessons that, while common to technology implementation, are especially critical in PRO implementation.

The effects of redesigning the IDEATel architecture on glucose uploads.

The objective of this evaluation was to determine the effect of redesigning the Informatics for Diabetes Education and Telemedicine (IDEATel) telemedicine architecture on the average upload delay and on the average number of glucose uploads to a central database. These two measures positively influence our ability to deliver timely and accurate patient care to the study population. The redesign was also undertaken to improve the patients' experience in using the system and thereby increase the frequency and timeliness of their self-monitoring behavior. Using the total number of glucose uploads, we compared the delay in glucose upload times according to the type of home telemedicine unit the study participants used and the region where the participants lived. The participants were Medicare beneficiaries with diabetes living in medically underserved neighborhoods in New York City and rural Upstate New York. The populations in these two regions differed considerably in terms of ethnicity, language spoken (Spanish, English), and education level. Participants who had Generation 2 (Gen 2) (mean = 10.75, SD +/- 7.96) home telemedicine units had significantly shorter upload delay times (p < 0.001) as measured in days than those participants with Generation 1 (Gen 1) (mean = 22.44, SD +/- 11.18) and those who were upgraded from Gen 1 (mean = 20.67, SD +/- 8.85) to Gen 2 (mean = 14.93, SD +/- 9.37). Additionally, the delay was significantly shorter for participants living upstate (mean = 24.14 days, SD +/- 11.95 days) than downstate (mean = 15.30 days, SD +/- 7.87 days), t (975) = 13.98, p < 0.01. The system redesign made a significant impact in reducing glucose upload delays of IDEATel participants. However, upload delays were significantly impacted by the region where the participants resided.

Pharmacogenomic clinical decision support design and multi-site process outcomes analysis in the eMERGE Network.

To better understand the real-world effects of pharmacogenomic (PGx) alerts, this study aimed to characterize alert design within the eMERGE Network, and to establish a method for sharing PGx alert response data for aggregate analysis. Seven eMERGE sites submitted design details and established an alert logging data dictionary. Six sites participated in a pilot study, sharing alert response data from their electronic health record systems. PGx alert design varied, with some consensus around the use of active, post-test alerts to convey Clinical Pharmacogenetics Implementation Consortium recommendations. Sites successfully shared response data, with wide variation in acceptance and follow rates. Results reflect the lack of standardization in PGx alert design. Standards and/or larger studies will be necessary to fully understand PGx impact. This study demonstrated a method for sharing PGx alert response data and established that variation in system design is a significant barrier for multi-site analyses.

Provider perspectives on the integration of patient-reported outcomes in an electronic health record.

OBJECTIVE: Integrating patient-reported outcomes (PROs) into electronic health records (EHRs) can improve patient-provider communication and delivery of care. However, new system implementation in health-care institutions is often accompanied by a change in clinical workflow and organizational culture. This study examines how well an EHR-integrated PRO system fits clinical workflows and individual needs of different provider groups within 2 clinics. MATERIALS AND METHODS: Northwestern Medicine developed and implemented an EHR-integrated PRO system within the orthopedics and oncology departments. We conducted interviews with 11 providers who had interacted with the system. Through thematic analysis, we synthesized themes regarding provider perspectives on clinical workflow, individual needs, and system features. RESULTS: Our findings show that EHR-integrated PROs facilitate targeted conversation with patients and automated triage for psychosocial care. However, physicians, psychosocial providers, and medical assistants faced different challenges in their use of the PRO system. Barriers mainly stemmed from a lack of actionable data, workflow disruption, technical issues, and a lack of incentives. DISCUSSION: This study sheds light on the ecosystem around EHR-integrated PRO systems (such as user needs and organizational factors). We present recommendations to address challenges facing PRO implementation, such as optimizing data collection and auto-referral processes, improving data visualizations, designing effective educational materials, and prioritizing the primary user group. CONCLUSION: PRO integration into routine care can be beneficial but also require effective technology design and workflow configuration to reach full potential use. This study provides insights into how patient-generated health data can be better integrated into clinical practice and care delivery processes.

An ancillary genomics system to support the return of pharmacogenomic results.

Existing approaches to managing genetic and genomic test results from external laboratories typically include filing of text reports within the electronic health record, making them unavailable in many cases for clinical decision support. Even when structured computable results are available, the lack of adopted standards requires considerations for processing the results into actionable knowledge, in addition to storage and management of the data. Here, we describe the design and implementation of an ancillary genomics system used to receive and process heterogeneous results from external laboratories, which returns a descriptive phenotype to the electronic health record in support of pharmacogenetic clinical decision support.

The REmote Patient Education in a Telemedicine Environment Architecture (REPETE).

The objective of the study was to develop and implement an architecture for remote training that can be used in the narrowband home telemedicine environment. A remote training architecture, the REmote Patient Education in a Telemedicine Environment (REPETE) architecture, using a remote control protocol (RCP) was developed. A set of design criteria was specified. The developed architecture was integrated into the IDEATel home telemedicine unit (HTU) and evaluated against these design criteria using a combination of technical and expert evaluations. Technical evaluation of the architecture demonstrated that remote cursor movements and positioning displayed on the HTU were smooth and effectively real-time. The trainers were able to observe within approximately 2 seconds lag what the patient sees on their HTU screen. Evaluation of the architecture by experts was favorable. Responses to a Likert scale questionnaire regarding audio quality and remote control performance indicated that the expert evaluators thought that the audio quality and remote control performance were adequate for remote training. All evaluators strongly agreed that the system would be useful for training patients. The REPETE architecture supports basic training needs over a narrowband dial-up connection. We were able to maintain an audio chat simultaneously with performing a remote training session, while maintaining both acceptable audio quality and remote control performance. The RCP provides a mechanism to provide training without requiring a trainer to go to the patient's home and effectively supports deictic referencing to on screen objects.

Biomedical informatics meets data science: current state and future directions for interaction.

There are an ever-increasing number of reports and commentaries that describe the challenges and opportunities associated with the use of big data and data science (DS) in the context of biomedical education, research, and practice. These publications argue that there are substantial benefits resulting from the use of data-centric approaches to solve complex biomedical problems, including an acceleration in the rate of scientific discovery, improved clinical decision making, and the ability to promote healthy behaviors at a population level. In addition, there is an aligned and emerging body of literature that describes the ethical, legal, and social issues that must be addressed to responsibly use big data in such contexts. At the same time, there has been growing recognition that the challenges and opportunities being attributed to the expansion in DS often parallel those experienced by the biomedical informatics community. Indeed, many informaticians would consider some of these issues relevant to the core theories and methods incumbent to the field of biomedical informatics science and practice. In response to this topic area, during the 2016 American College of Medical Informatics Winter Symposium, a series of presentations and focus group discussions intended to define the current state and identify future directions for interaction and collaboration between people who identify themselves as working on big data, DS, and biomedical informatics were conducted. We provide a perspective concerning these discussions and the outcomes of that meeting, and also present a set of recommendations that we have generated in response to a thematic analysis of those same outcomes. Ultimately, this report is intended to: (1) summarize the key issues currently being discussed by the biomedical informatics community as it seeks to better understand how to constructively interact with the emerging biomedical big data and DS fields; and (2) propose a framework and agenda that can serve to advance this type of constructive interaction, with mutual benefit accruing to both fields.

Conceptual knowledge acquisition in biomedicine: A methodological review.

The use of conceptual knowledge collections or structures within the biomedical domain is pervasive, spanning a variety of applications including controlled terminologies, semantic networks, ontologies, and database schemas. A number of theoretical constructs and practical methods or techniques support the development and evaluation of conceptual knowledge collections. This review will provide an overview of the current state of knowledge concerning conceptual knowledge acquisition, drawing from multiple contributing academic disciplines such as biomedicine, computer science, cognitive science, education, linguistics, semiotics, and psychology. In addition, multiple taxonomic approaches to the description and selection of conceptual knowledge acquisition and evaluation techniques will be proposed in order to partially address the apparent fragmentation of the current literature concerning this domain.

Mapping the evolving definitions of translational research.

OBJECTIVE: Systematic review and analysis of definitions of translational research. MATERIALS AND METHODS: The final corpus was comprised of 33 papers, each read by at least 2 reviewers. Definitions were mapped to a common set of research processes for presentation and analysis. Influence of papers and definitions was further evaluated using citation analysis and agglomerative clustering. RESULTS: All definitions were mapped to common research processes, revealing most common labels for each process. Agglomerative clustering revealed 3 broad families of definitions. Citation analysis showed that the originating paper of each family has been cited ~10 times more than any other member. DISCUSSION: Although there is little agreement between definitions, we were able to identify an emerging consensus 5-phase (T0-T4) definition for translational research. T1 involves processes that bring ideas from basic research through early testing in humans. T2 involves the establishment of effectiveness in humans and clinical guidelines. T3 primarily focuses on implementation and dissemination research while T4 focuses on outcomes and effectiveness in populations. T0 involves research such as genome-wide association studies which wrap back around to basic research. CONCLUSION: We used systematic review and analysis to identify emerging consensus between definitions of translational research phases.

Design features of graphs in health risk communication: a systematic review.

This review describes recent experimental and focus group research on graphics as a method of communication about quantitative health risks. Some of the studies discussed in this review assessed effect of graphs on quantitative reasoning, others assessed effects on behavior or behavioral intentions, and still others assessed viewers' likes and dislikes. Graphical features that improve the accuracy of quantitative reasoning appear to differ from the features most likely to alter behavior or intentions. For example, graphs that make part-to-whole relationships available visually may help people attend to the relationship between the numerator (the number of people affected by a hazard) and the denominator (the entire population at risk), whereas graphs that show only the numerator appear to inflate the perceived risk and may induce risk-averse behavior. Viewers often preferred design features such as visual simplicity and familiarity that were not associated with accurate quantitative judgments. Communicators should not assume that all graphics are more intuitive than text; many of the studies found that patients' interpretations of the graphics were dependent upon expertise or instruction. Potentially useful directions for continuing research include interactions with educational level and numeracy and successful ways to communicate uncertainty about risk.

Quantifying visual similarity in clinical iconic graphics.

OBJECTIVE: The use of icons and other graphical components in user interfaces has become nearly ubiquitous. The interpretation of such icons is based on the assumption that different users perceive the shapes similarly. At the most basic level, different users must agree on which shapes are similar and which are different. If this similarity can be measured, it may be usable as the basis to design better icons. DESIGN: The purpose of this study was to evaluate a novel method for categorizing the visual similarity of graphical primitives, called Presentation Discovery, in the domain of mammography. Six domain experts were given 50 common textual mammography findings and asked to draw how they would represent those findings graphically. Nondomain experts sorted the resulting graphics into groups based on their visual characteristics. The resulting groups were then analyzed using traditional statistics and hypothesis discovery tools. Strength of agreement was evaluated using computational simulations of sorting behavior. MEASUREMENTS: Sorter agreement was measured at both the individual graphical and concept-group levels using a novel simulation-based method. "Consensus clusters" of graphics were derived using a hierarchical clustering algorithm. RESULTS: The multiple sorters were able to reliably group graphics into similar groups that strongly correlated with underlying domain concepts. Visual inspection of the resulting consensus clusters indicated that graphical primitives that could be informative in the design of icons were present. CONCLUSION: The method described provides a rigorous alternative to intuitive design processes frequently employed in the design of icons and other graphical interface components.